NPHP3 p.Cys704=
c.2112T>C · rs761833505 · VCV1029228
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.01%, amr)
Conditions
2
NPHP3-related Meckel-like syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.1 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 9.253 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/60,030 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.000434%
7/1,614,126 alleles · very rare
exomes 7/1,461,772 · genomes 0/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 10,005 |
| European (non-Finnish) | 8.47e-05% | 1,180,011 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- NPHP3
- Protein
- p.Cys704=
- Coding
- c.2112T>C
- MANE Select
- NM_153240
- dbSNP
- rs761833505
- Type
- single nucleotide variant
- Location
- chr3:132696790 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.59 · 1 PDB
Similar variants
- NPHP3 p.Cys704fs Pathogenic ★ same residue
- NPHP3 p.Cys704Arg Uncertain significance ⚠ same residue
- NPHP3 c.1985+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NPHP3 c.3201+1G>T Likely pathogenic ★★ same condition
- NPHP3 c.393+1G>C Likely pathogenic ★★ same condition
- NPHP3 c.520-1G>T Pathogenic ★★ same condition
- NPHP3 c.823+1G>T Likely pathogenic ★★ same condition
- NPHP3 c.958-2A>G Pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/nphp3-p-cys704 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown